We believe that a major strength of Stanford University in this application is its prior interest in treating chronic viral infections which has led to expertise in areas such as virology, viral immunology and pharmacology as well as extensive clinical trials experience. Therefore, it is expected that our group can continue to generate new relevant technology and be involved in ACTG committees such as HlV Disease, Pharmacology, Site and Data Management, Protocol Evaluation, Virology and lmmunology. Thus we can continue to produce innovative Phase I and Phase II efforts with newly available agents as well as be involved in NDA oriented Phase Ill trials. We will continue to work with kaiser Foundation Hospital in San Francisco and the AIDS Clinical Research Consortium with satellite units at Santa Clara and San Mateo County Hospitals. The latter will particularly help our minority and female involvement and bring more IV-drug users and disadvantaged people into our program. Our highly experienced staff can be relied on to produce high quality clinical data and most efficiently utilize our resources to maximize our enrollment and retain patients in all types of trials. We expect to continue to perfect methods of drug administration including improved methodology for individualization of therapies in regard to both chemo and immuno therapy. Therefore the virology and immunology labs are central to our efforts and cover both molecular and cell biological methodology in determining drug or immunomodulator action and sensitivity. Many useful new clinical monitoring methods have been pioneered in our lab and we expect to continue to play that role in the new ACTG configuration. Hopefully, we will be able to use the molecular insights gained in regard to the impact of various drugs or vaccines on the therapeutic targets within the virus to minimize the impact of drug resistance changes and potentially avoid the development viral immune escape mutants. To this end our methods of measuring specific epitope directed cytotoxic T cell reactivity by rapidly examining viral target genes will help us see whether some of the allogenic immune cell based methodology we are developing with our NIAID sponsored SPIRAT grant can be transferred to the ACTG for wider scale testing. Our present work with high dose Roche protease and other upcoming antiviral efforts which are privately sponsored will also give us insights to analyze the impact of such inhibitors which can then be applied to patients in ACTG trials. We expect that other targets like the integrase and/or various regulatory genes could also be important targets for chemotherapy in the years to come. We expect to be able to adapt our present methods for viral load measurement and rapid analysis of genotypes within viral target genes to be useful in that upcoming work. We intend to continue to bring innovative clinical science to bear on infection but also must continue our patient focus on bringing more women and more minorities into our program as the epidemic changes its pattern making these groups the major target of infection. Our pharmacology group plans to bring together quantitative viral markers with careful quantitative virologic measurements, so as to do more effectively individualize therapy within patients. Given our new units in primary care at Stanford and our groups involvement with the major supplier of primary HIV care to Santa Clara and San Mateo Counties, we expect to be able to enter more patients into opportunistic infection and oncology protocols as well.